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РЖ ВИНИТИ 34 (BI48) 95.10-04Т1.317

Margineanu, D.
UCB L059, a novel anticonvulsant, reduces bicuculline-induced neuronal hyperexcitability, possibly through Ca-dependent mechanisms [Text] : [Pap.] 1st Eur. Congr. Pharmacol., Milan, June 16-19, 1995 / D. Margineanu, E. Wulfert // Pharmacol. Res. - 1995. - Vol. 31, Suppl. - P347 . - ISSN 1043-6618
Перевод заглавия: ucb L059, новое противосудорожное средство, уменьшает вызываемую бикукуллином повышенную возбудимость нейронов, возможно, с помощью Ca-зависимых механизмов
Аннотация: Orthodromic field population spikes (PS[2]), elicited upon commissural stimulation in the hippocampal CA3 region of anaesthitized rat, were increased when the recording micropipette contained either bicuculline or bicuculline methiodide (BIC, 8 mM). The BIC-induced increase in PS[2] was consistently reduced at all stimulation intensities tested, by the novel anticonvulsant drug ucb LO59 ((S)='альфа' ethyl-2-oxo-1-pyrrolidine acetamide, 3.2 * 10{-5} mol/kg iv or 4 umol/kg icv), when injected before lowering in place the BIC-containing micropipette. Stimulus intensities ranged from 0.25 to 6 mA, ucb L059 did not affect baseline PS[2] responses in the absence of BIC. BIC reduced low-interstimulus interval (ISI) inhibition in paired pulse experiments. ucb L059 reduced the BIC-induced increase in amplitude of the responses to both of thepaired pulses, without influencing BIC-induced reduction of los-ISI inhibition. These results suggest that reduction of the BIC-induced increase in neuronal excitability by ucb L059 may occur via non GABAergic mechanisms. Verapamil (0.4 'мю'mol/kg icv) and ethosuximide (2 mmol/kg iv) reduced BIC-induced increase in PS[2] but only at low stimulus strength (1 mA), while valproate (20 mg/kg iv) and carbamazepine (20 mg/kg ip) reduced PS[2] increase only at high stimulus strength ( 3 mA). The profile of the anti-BIC effect of ucb L059 was best mimicked by flunarizine (50 'мю'mol/kg ip). These results suggest that ucb L059 may antagonize an extra-synaptic, possibly Ca{2+}-mediated increase in hippocampal pyramidal neurones excitability, produced by bicuculine. Бельгия, UCB SA Pharma Sector, Res. & Devel., Chemin du Foriest, B-1420 Braine-l'Alleud

ГРНТИ	34.45.21

ВИНИТИ 341.45.21.15.69
Рубрики: UCB L059
ГИППОКАМАП
ОБЛАСТЬ CA3
ВОЗБУДИМОСТЬ НЕЙРОНОВ
БИКУКУЛЛИН
КАЛЬЦИЙ-ЗАВИСИМЫЕ МЕХАНИЗМЫ
КРЫСЫ

Доп.точки доступа:
Wulfert, E.

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